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The Epiphyseal Growth Plate: The Engine That Drives Bone Elongation

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Handbook of Growth and Growth Monitoring in Health and Disease

Abstract

The goal of this chapter is to analyze the functional and molecular significance of the growth cartilage and to consider how this tissue, as a functional unit, promotes regulated bone growth. The epiphyseal growth plate comprises a thin film of transient cartilage that is most often located between the diaphysis and the secondary center of ossification. It contains just one cell type, chondrocytes; these cells undergo a complex differentiation process and secrete an abundant extracellular matrix. In this review, attention is directed at considering the unique structure of the growth plate itself and the associated bone, while considerable emphasis is placed on assessing the life history and function of the resident cells. Initially, chondrocytes within the growth plate undergo several rounds of proliferation and secrete a complex extracellular matrix that contains structural proteins, proteoglycans, and bioactive growth factors; when the replicative phase has ceased, chondrocytes increase their volume and undergo terminal differentiation. During this period, they continue to synthesize a unique extracellular matrix, undergo a shape change, bud-off matrix vesicles, and generate foci of mineral which eventually coalesce with other mineral deposits to form calcified cartilage. In this latter phase of their life history, the post-mitotic hypertrophic chondrocytes express an autophagic phenotype. Subsequently, these terminally differentiated chondrocytes are deleted from the plate by induction of the apoptotic process. The mineralized septa are then used as sites for deposition of bone mineral by osteoblasts, which then form many of the trabeculae of the underlying metaphyseal bone. In the review, considerable emphasis is placed on the mechanism by which the hypertrophic cell generates the space for new bone formation. Finally, following a discussion of the cellular and molecular characteristics of the growth plate, especially the mode of survival of cells in their hypoxic microenvironment, the mechanism by which growth factors regulate proliferation and hypertrophy is discussed.

Vickram Srinivas: Deceased

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Notes

  1. 1.

    An apt description of the overall architecture of one of the authors of this review.

  2. 2.

    Not to be confused with the metallica rock group Nodes of Ranvier from South Carolina.

  3. 3.

    According to Wikipedia, in Canada, the United States, and South Africa, a flapjack is a thin and crispy but slightly chewy pancake. Its defining attribute is its large diameter, commonly measuring 25 cm or more. Not to be confused with the British flapjack which is a baked bar biscuit, made from rolled oats, butter, and brown sugar and usually served with Golden syrup or honey.

  4. 4.

    Not be confused with Paraechinus micropus which can be distinguished from other hedgehogs by its raccoon-like face.

  5. 5.

    Indeed, these cells do not generate CO2. Hence, from the perspective of environmental sustainability, the growth cartilage is exemplary. Decreased generation of gases by other tissues would help address problems associated with degradation of the ozone layer.

Abbreviations

AMPkinase:

Adenosine monophosphate kinase

Bcl2:

B cell leukemia protein 2

BMP:

Bone morphogenetic protein

BNIP3:

BCL2/adenovirus E1B 19 kDa interacting protein 3

BrdU:

Bromodeoxyuridine

Ca2+ :

Calcium ion

COMP:

Cartilage oligomeric protein

ERK1/2:

Extracellular signal-regulated kinase 1/2

FGF:

Fibroblast growth factor

FGF(R):

Fibroblast growth factor receptor

HDAC:

Histone deacetylase

HIF:

Hypoxia-inducible factor

IHH:

Indian hedgehog

LC-3:

Microtubule-associated light chain protein-3

MAPK:

Mitogen-activated protein kinase

MMP:

Matrix metalloproteinase

NO:

Nitric oxide

PHD:

Prolyl hydroxylase

Pi:

Phosphate ion

PKC:

Protein kinase C

PTHrp:

Parathyroid hormone-related protein

ROS:

Reactive oxygen species

STAT:

Signal transducers and activators of transcription proteins

TGF:

Transforming growth factor

TIMP:

Tissue inhibitor of matrix metalloproteinase

VEGF:

Vascular endothelial growth factor

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Acknowledgments

The authors acknowledge the contract grant sponsor National Institutes of Health DE 015694 and DE 016383 (to VS) and DE 010875 and DE 013319 (to IMS).

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Jefferson Medical College, Philadelphia, PA, 19107, USA

    Vickram Srinivas & Irving M. Shapiro

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  1. Vickram Srinivas
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Correspondence to Irving M. Shapiro .

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Editors and Affiliations

  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

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Srinivas, V., Shapiro, I.M. (2012). The Epiphyseal Growth Plate: The Engine That Drives Bone Elongation. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_80

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